We plan to complete our studies on the microregional distribution of myo- and scyllo-inositols in cat cochlear nucleus. We will study the effects of lithium and cholinergic agonists on inositol metabolism, measuring changes in levels of myo-inositol, myo-inositol 1-phosphate, and if possible, myo-inositol 1,2-cyclic-phosphate caused by these drugs in rat cerebral cortex layers. The effects of osmotic stress and of the estrous cycle in rats will be studied in hypothalamic nuclei and in pituitary to find if changes in myo-inositol and other products of the hydrolysis of phosphatidylinositol occur under these stimuli. To this end we will try to develop a method for the measurement of diglyceride and phosphatidic acid using gas chromotography-mass spectrometry. We plan to study the transport and synthesis of myo- and scyllo-inositol in pancreatic islets and the effect of these inositols on insulin secretion. We will continue our studies on the myo-inositol oxidoreductase and scyllo-inositol oxidoreductase we have isolated from brain tissue to learn more about their function. We hope to prepare fluorescent antibodies to these enzymes so as to localize them in the nervous system. These studies should lead to a better understanding of the function of scyllo-inositol in mammals. The purification of L-myo-inositol 1-phosphate synthase will be continued in an effort to obtain it homogeneous. We expect to learn the meaning of the apparent heterogeneity of this enzyme, to find the means by which the myo-inositol synthetic pathway is regulated in vivo and to better understand the mechanism by which the enzyme synthesizes myo-inositol-1-P. We are also studying the phosphatase which converts myo-1-P to free myo-inositol with respect to its inhibition by lithium. If possible we will ultimately prepare fluorescent antibodies to both of the myo-inositol pathway enzymes so as to localize them in tissues.